The incidence of cerebral vascular disease in patients with long-standing diabetes makes an understanding of the chemical and morphological basis of the underlying lesions of major importance. Studies of basement membrane composition and structure in the cerebral vessels in diabetes have been neglected. The possible association of these lesions with chemical alterations in the basement membrane of the brain vessels call for detailed biochemical analysis. The overall aim of this research project is to investigate the nature and structural basis for the basement membrane alterations in the human cerebral microvasculature in diabetes. The main questions to be answered are the following: 1. Are there differences in the amino acid and carbohydrate composition of brain vessel basement membranes from normal and diabetic human subjects? 2. Are there qualitative and quantitative changes in the glycoprotein and collagenous components of brain vessel basement membranes in diabetes? 3. Is the crosslinking of the basement membrane altered in brain vessels from diabetic subjects? 4. Is there a correlation between the degree and nature of cerebral vascular complications, basement membrane thickening and the composition and structure of the basement membrane? 5. Can the chemical and morphological abnormalities of the microvasculature be correlated with atherosclerosis, parenchymal disease (infarction) and skeletal muscle basement membrane changes? 6. Do these abnormalities correlate with the severity of the diabetes or with accompanying conditions such as hypertension or advanced age? The answers to these questions will be sought by the isolation, analysis and fractionation of microvessels and basement membranes from human brain obtained post mortem in a newly developed and recently published procedure.